IntraIndividual Variability in Serum Alpha-1 Antitrypsin Levels.

Annie Haillot,Ronald J Dandurand,François Maltais,Andrée-Anne Pelland,Yohan Bossé,Tomás P Carroll

doi:10.15326/jcopdf.2021.0228

Abstract

Measuring alpha-1 antitrypsin (AAT) serum levels is often the first step when investigating for alpha-1 antitrypsin deficiency (AATD). The purpose of this study was to determine the test-retest reproducibility of AAT serum levels and to determine if between-measurements variability was associated with acute phase markers of inflammation. We retrospectively analyzed a sample of 255 patients from a community respirology practice with chronic obstructive pulmonary disease (COPD) in whom AAT serum levels were measured twice, on separate visits. White blood cell count and fibrinogen were also measured at the time of the second blood sampling as markers of acute phase inflammation. Intraclass correlation coefficient (ICC), Pearson correlation coefficient, and Bland-Altman analysis were used to document test-retest reproducibility. Regression analyses were used to identify potential correlates of test-retest AAT level differences. Although the 2 AAT serum levels were significantly correlated, the between-measurement agreement was weak (ICC of 0.38 [95% confidence interval (CI), 0.27 to 0.48]; Pearson correlation coefficient of 0.34 [95% CI, 0.23 to 0.44]) and Bland-Altman analysis revealed wide 95% limits of agreement. Considering that an AAT serum level below 1.13g/L should trigger further investigations to confirm the AAT status, discrepancies between the test-retest AAT levels resulted in reconsidering requirement for further investigation in 22% of patients. A significant correlation between the fibrinogen value and the second AAT level was found (r=0.21, p=0.004 [n=173]). Serum AAT levels showed weak intra-individual reproducibility which could lead to AATD status misclassification and potentially a missed diagnosis of AATD.

Highlights

Alpha-1 antitrypsin (AAT) is a serine proteinase inhibitor[1] whose major function is to inhibit neutrophil elastase.[2]
The purpose of this study was to determine the testretest reproducibility of alpha-1 antitrypsin (AAT) serum levels and to identify potential correlates of test-retest differences in AAT levels such as acute phase inflammation, time elapsed between measurements, laboratory where the measurement was done, individual characteristics, and pulmonary function data
Study Design We performed a retrospective analysis of a convenience sample of 255 patients with chronic obstructive pulmonary disease (COPD) who were offered AAT quantification by nephelometry following the World Health Organization (WHO) and ATS/ERS recommendations and in whom serum AAT levels were measured at least twice, on separate patient visits between 2010 and 2014, irrespective of baseline characteristics, degree of suspicion of alpha-1 antitrypsin deficiency (AATD), or AAT level on the first measurement

Summary

Introduction

Alpha-1 antitrypsin (AAT) is a serine proteinase inhibitor[1] whose major function is to inhibit neutrophil elastase.[2] When AAT is deficient, unopposed neutrophil elastase can attack fragile alveolar tissue, and the repetitive proteolytic insults eventually cause emphysema.[3] Alpha-1 antitrypsin deficiency (AATD) was first described in 1963 by Laurell and Erikson.[4] It is the most common cause of hereditary chronic obstructive pulmonary disease (COPD) affecting up to 5% of people with the disease when severe and intermediate AATD is included.[5,6] AATD is inherited in an autosomal codominant fashion.

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